Figure 8. Repetitive application of a TLR7 agonist (R848) to the skin activates tissue macrophages which signal to the bone marrow to drive the expansion of haematopoietic stem and progenitor cells (HSPCs) and their differentiation into monocytes.

These Ly6C-high monocytes have an immature phenotype and egress from the bone marrow independently of CCR2. Subsequently, Ly6C-high monocytes differentiate into Ly6C-low blood monocytes and into tissue macrophages in multiple organs such as liver, lung, and kidneys. When challenged with a secondary viral stimulus such as influenza or respiratory syncytial virus (RSV) infection, the emergency myelopoiesis is associated with reduced disease severity.